Effect of SOCS1 Gene on Growth Inhibition of Acute Myeloid Leukemia Cells Mediated by JAK2/STAT Signaling Pathway

Abstract

To explore the correlation of SOCS1 gene methylation with the activity of JAK2/STAT signaling pathway, genesis and progress of acute myeloid leukemia. Several techniques, such as cell culture, qPCR, MS-PCR, Western bolt, CCK-8 assay, flow cytometry and gene transfection were used to analyze the relation of expression and methylation statues of SOCS1 gene with the genesis and progression of AML in 120 AML patients and leukemia cell lines U937 and THP-1, at the same time to analyze the changes of downstream protein expression in JAK2/STAT signaling pathway and their effect on the growth and apoptosis of leukemia cell lines. The positive rate of WT1/ABL in SOCS1 methylated group was significantly higher than that in SOCS1 non-methylated group, and the complete remission rate of one course treatment in SOCS1-methylated group was significantly lower than that in SOCS1 non-methylated group. The expression level of SOCS1 gene in low methylation rate group was higher, and the expression of down-stream proteins p-JAK2, p-STAT3 and p-STAT5 in JAK2/STAT signaling pathway decreased, while the expression of t-JAK2,t-STAT3 and t-STAT5 was not changed statistically significantly. The growth rate of leukemia cells graduated decreased, and the apoptosis rate of leukemia cells graduated increased along with the enhancement of methylation drug concentration. The methylation of SOCS1 gene results in the gene silencing, thereby declines its inhibition on the down-stream proteins in JAK2/STAT signaling pathway, and finally promotes the growth and proliferation of AML cells.